PROJECT SUMMARY/ABSTRACT Pulmonary hypertension (PH) is a devastating disease that often co-exists with lung disease, such as chronic obstructive pulmonary disease (COPD). This combination is a major cause of morbidity and mortality, and millions of Americans with COPD are at risk. Identifying populations with early PH, who might benefit most from screening and treatment, could reduce this impact. Unfortunately, the gold-standard method of detecting PH is right heart catheterization, a costly, invasive procedure that is not practical for large-scale clinical use. Image analysis has been used in research settings to quantify PH-related vascular changes, such as ?pruning,? using computed tomography (CT). Pruning on CT is associated with cardiopulmonary impairment and PH severity in COPD-specific research cohorts; however, little is known about cardiopulmonary manifestations of pruning in healthier populations that may benefit from screening, and it is also unclear how protocol differences between research and clinical CTs impact the technical feasibility of using this measure in a clinical context. The key focus of this project is to advance the translation of this research-based tool into a bedside role by evaluating cardiopulmonary implications of this imaging biomarker in a healthier population at risk for lung disease and PH, and by demonstrating feasibility in clinically acquired CT data. Using data from the generally healthy Framingham Heart Study, the first aim will investigate associations of radiographic pulmonary vascular measures with indicators of pulmonary and right heart dysfunction, while the second will clarify the influence of left heart dysfunction (also a cause of PH) on this radiographic measure. This work will be accomplished by the application of advanced epidemiologic methods, including linear and nonlinear multivariable modeling and interaction analyses. The third aim is a feasibility study applying research-based vascular image analysis to clinically acquired CT scans in a cohort of COPD patients, which will involve modular image processing methods, manipulation of software algorithms, original data generation, and quality assurance procedures. This work will inform the clinical interpretation and translational potential of pulmonary vascular image analysis, and may ultimately improve the clinical approach to patients at risk for PH, including those with lung disease. This project is supported by an outstanding, multidisciplinary team of experts who will provide rigorous training, complemented by formal coursework, for all aspects of the proposed work, as well as mentored career development. The project will be based primarily within the Institute for Lung Health at Beth Israel Deaconess Medical Center, with support from the Harvard School of Public Health, the Applied Chest Imaging Laboratory at Brigham and Women?s Hospital, Harvard Medical School, and the Harvard Combined Pulmonary Fellowship Program, forming a robust environment with unique resources to support the proposed training and research.